Caixianghai research group of Kunming Institute of botany has made new progress in the study of monoterpene indole alkaloids

Monoterpenoid indole alkaloids have the characteristics of complex structure and high drug yield, which have been the focus of natural pharmaceutical chemistry research Up to now, about 3000 alkaloids have been reported, including dozens of clinical drugs, such as vinblastine, camptothecin, quinine, strychnine, rose tree alkaloids, etc The resources of monoterpene indole alkaloids are the most abundant in Southwest China, which is a valuable resource for alkaloid research Cai Xianghai research group, Yunnan characteristic plant resources utilization and development team, State Key Laboratory of Phytochemistry and sustainable utilization of Western plant resources, Kunming Institute of Botany, Chinese Academy of Sciences, has been committed to the research of monoterpene indole alkaloids, and has made new progress in recent research The research team carried out a systematic study on the alkaloids of Tabernaemontana bovina Wu Jing, a doctoral candidate, used HPLC-UV to guide the separation and found four unique conjugated monoterpenoid quinoline alkaloids taberbovines A-D from its stem, which had the structural characteristics of 6 / 6 / 5 / 6 / 5 ring system (Fig 1) The structures of these alkaloids were determined by NMR, X-ray diffraction, CGC and NMR, and the possible sources were speculated (Fig 2) The research results were published on the topic of "four yellow monoterpenoid quinoline alkaloids from the steps of Tabernaemontana bovina" in organic letters (organic letters 2019, 21, 4554-4558) Fig 1 the structure of taberbovines A-D and its UV spectrum (source: Organic letters 2019, 21, 4554-4558) Fig 2 the possible source pathway of taberbovines A-D skeleton (source: Organic letters 2019, 21, 4554-4558) it is generally believed that the only precursor of monoterpenoid indole alkaloids is strigoside produced by the condensation of tryptamine and secloganin In 2011, the research team found alstrostine a (org Lett 2011, 13, 3568) formed by the condensation of tryptophan and strychnine in a ratio of 1:2 In recent studies, Yu Yang, a doctoral student, discovered the alkaloid tabernabovine a from the leaves of medicinal dogtooth flowers The molecule was condensed by tryptophan in a ratio of 2:1 with strychnine (Fig 3) The above results support the diversity of monoterpene indole alkaloids At the same time, the novel skeleton alkaloids tabernabovine B and C were also found Tabernabowene B is a cage like compound formed by many bridge rings, and tabernabowene C is an indole oxide alkaloid with skeleton rearrangement The above alkaloid structure is also supported by NMR, x-single crystal diffraction, computational circular dichroism and NMR, and the biogenic process of tabernabovine B-C is speculated (Fig 4) The above research results are also published on organic letters (organic letters 2019, 21, 5938-5942) under the title of "tabernabovines a – C: three monotectoid indole alkaloids from the leaves of Tabernaemontana bovina" Figure 3 tabernabovines A-D structural formula (source: Organic letters 2019, 21, 5938-5942) Figure 4 taberbovine B possible source pathway (source: Organic letters 2019, 21, 5938-5942) Figure 5 taberbovine C possible source pathway (source: Organic letters 2019, 21, 5938-5942) In addition, Shi Baobao, a doctoral student, found 78 alkaloids in t bufalina It is worth mentioning that compound apparicine has a strong inhibitory effect on xanthine oxidase (IC50 = 0.65 μ m) (Figure 5), which is equivalent to the activity of allopurinol, the first-line drug for gout (IC50 = 0.60 μ m) The research results were published on phytochemistry (DOI: 10.1016 / j.phytochem 2019.112060) under the title of "alkaloids isolated from Tabernaemontana bufalina display xanthine oxide endogenous activity" Fig 6 Molecular Simulation of inhibition of xanthine oxidase (1n5x) by apparicine (source: Phytochemistry)